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I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma

BACKGROUND: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy w...

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Autores principales: Carrasquillo, Jorge A., O’Donoghue, Joseph A., Beylergil, Volkan, Ruan, Shutian, Pandit-Taskar, Neeta, Larson, Steven M., Smith-Jones, Peter M., Lyashchenko, Serge K., Ohishi, Norihisa, Ohtomo, Toshihiko, Abou-Alfa, Ghassan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838028/
https://www.ncbi.nlm.nih.gov/pubmed/29508107
http://dx.doi.org/10.1186/s13550-018-0374-8
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author Carrasquillo, Jorge A.
O’Donoghue, Joseph A.
Beylergil, Volkan
Ruan, Shutian
Pandit-Taskar, Neeta
Larson, Steven M.
Smith-Jones, Peter M.
Lyashchenko, Serge K.
Ohishi, Norihisa
Ohtomo, Toshihiko
Abou-Alfa, Ghassan K.
author_facet Carrasquillo, Jorge A.
O’Donoghue, Joseph A.
Beylergil, Volkan
Ruan, Shutian
Pandit-Taskar, Neeta
Larson, Steven M.
Smith-Jones, Peter M.
Lyashchenko, Serge K.
Ohishi, Norihisa
Ohtomo, Toshihiko
Abou-Alfa, Ghassan K.
author_sort Carrasquillo, Jorge A.
collection PubMed
description BACKGROUND: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen. Serial positron emission tomography (PET) imaging and pharmacokinetics were performed following I-124 codrituzumab. An ELISA assay was used to determine “cold” codrituzumab serum pharmacokinetics and compare it to that of I-124 codrituzumab. Correlation of imaging results was performed with IHC. Short-term safety assessment was also evaluated. RESULTS: Thirteen patients had tumor localization on baseline I-124 codrituzumab; heterogeneity in tumor uptake was noted. In three patients undergoing repeat imaging while on immunotherapy/sorafenib, evidence of decreased I-124 codrituzumab uptake was noted. All three patients who underwent imaging after progression while on immunotherapy continued to have I-124 codrituzumab tumor uptake. Pharmacokinetics of I-124 codrituzumab was similar to that of other intact IgG. No significant adverse events were observed related to the I-124 codrituzumab. CONCLUSIONS: I-124 codrituzumab detected tumor localization in most patients with HCC. Pharmacokinetics was similar to that of other intact iodinated humanized IgG. No visible cross-reactivity with normal organs was observed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-018-0374-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-58380282018-03-12 I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma Carrasquillo, Jorge A. O’Donoghue, Joseph A. Beylergil, Volkan Ruan, Shutian Pandit-Taskar, Neeta Larson, Steven M. Smith-Jones, Peter M. Lyashchenko, Serge K. Ohishi, Norihisa Ohtomo, Toshihiko Abou-Alfa, Ghassan K. EJNMMI Res Original Research BACKGROUND: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen. Serial positron emission tomography (PET) imaging and pharmacokinetics were performed following I-124 codrituzumab. An ELISA assay was used to determine “cold” codrituzumab serum pharmacokinetics and compare it to that of I-124 codrituzumab. Correlation of imaging results was performed with IHC. Short-term safety assessment was also evaluated. RESULTS: Thirteen patients had tumor localization on baseline I-124 codrituzumab; heterogeneity in tumor uptake was noted. In three patients undergoing repeat imaging while on immunotherapy/sorafenib, evidence of decreased I-124 codrituzumab uptake was noted. All three patients who underwent imaging after progression while on immunotherapy continued to have I-124 codrituzumab tumor uptake. Pharmacokinetics of I-124 codrituzumab was similar to that of other intact IgG. No significant adverse events were observed related to the I-124 codrituzumab. CONCLUSIONS: I-124 codrituzumab detected tumor localization in most patients with HCC. Pharmacokinetics was similar to that of other intact iodinated humanized IgG. No visible cross-reactivity with normal organs was observed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-018-0374-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-03-05 /pmc/articles/PMC5838028/ /pubmed/29508107 http://dx.doi.org/10.1186/s13550-018-0374-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Carrasquillo, Jorge A.
O’Donoghue, Joseph A.
Beylergil, Volkan
Ruan, Shutian
Pandit-Taskar, Neeta
Larson, Steven M.
Smith-Jones, Peter M.
Lyashchenko, Serge K.
Ohishi, Norihisa
Ohtomo, Toshihiko
Abou-Alfa, Ghassan K.
I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
title I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
title_full I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
title_fullStr I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
title_full_unstemmed I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
title_short I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
title_sort i-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838028/
https://www.ncbi.nlm.nih.gov/pubmed/29508107
http://dx.doi.org/10.1186/s13550-018-0374-8
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